Nitrogen Balance as Affected by Neoplastic Disease and Its Therapy

Abstract

Normal subjects and those ill with chronic non-neoplastic diseases stored nitrogen when fed an adequate diet in a metabolic study unit; however, patients with active neoplastic disease demonstrated nitrogen equilibrium, positive nitrogen balance or negative nitrogen balance when studied under identical conditions. Examples of variations in nitrogen metabolism in patients with neoplastic disease are shown by studies in four patients with chronic myelocytic leukemia: (1) The first was in negative calorie balance but nitrogen equilibrium while eating a diet adequate in protein; later, following a course of chemotherapy, he showed increased nitrogen retention. (2) The second was unable to retain nitrogen while under study even following remission but gained weight rapidly after returning home. (3) The third demonstrated nitrogen retention despite weight loss and negative calorie balance. (4) The fourth displayed the metabolic changes occurring during relapse in the form of a "blastic crisis." To distinguish in quantitative terms between active and inactive neoplastic disease and to appraise the effects of varying the caloric and protein contents of the diet, a patient with lymphosarcoma was studied by classic metabolic balance and by N¹⁵-labeled l-aspartic acid kinetic methods. Only on the high calorie, high protein diet did her nitrogen incorporation into protein increase, but even then her net nitrogen retention was no greater than on the lower protein and calorie diets. Later, in a more active phase of her disease, the patient showed increased nitrogen incorporation into protein, even though the diet was low both in calories and in protein. These findings suggest (1) that increased protein turnover may be an essential prelude to positive nitrogen balance and (2) that high protein and calorie dietary intakes during an active phase of neoplastic disease when protein turnover is already high may merely increase energy and protein metabolism without inducing net nitrogen retention. The need for better and simpler technology and for more studies of the details of human nitrogen metabolism is emphasized by the numerous gaps in present knowledge pointed out by these investigations.